Evolution of definitive external beam radiation therapy in the treatment of prostate cancer

Abstract

Purpose: Although the clinical significance of a diagnosis of prostate cancer for some men is debated, for many men it leads to significant morbidity and mortality. Radical treatment of clinically localized prostate cancer has been shown to improve survival in men with intermediate or high-risk disease. There is no high level evidence to support the superiority of radical prostatectomy, with or without adjuvant or salvage external beam radiotherapy in comparison to definitive radiotherapy with or without androgen deprivation, and the choice should be individualized. External beam radiation therapy practices are in constant evolution, and numerous strategies have been investigated to improve either efficacy or reduce toxicity, or both.

Methods: Randomized controlled trials investigating strategies to improve efficacy, reduce toxicity, or both of external beam radiotherapy have been reviewed in men with prostate cancer without nodal or distant metastases. These strategies include the use of neo-adjuvant and adjuvant androgen deprivation, dose-escalation, hypofractionation, whole pelvic radiation therapy, incorporation of improved imaging, image- guided radiation therapy, and adjuvant systemic therapy. The evidence to date for these strategies is discussed, noting limitations in applying the results of reported trials to men treated in contemporary settings.

Results: A number of strategies have shown improvements in biochemical control using external beam radiotherapy. To date, only with the use of androgen deprivation therapy has this translated into improvements in disease specific and overall survival. This may reflect the long natural history of prostate cancer and high incidence of competing risks. Technological advances have enabled dose escalation with reduced toxicity, of paramount importance given the long natural history.

Results: The use of external beam radiation therapy in prostate cancer is evolving with numerous strategies incorporated to improve outcomes. The optimum dose and fractionation and use of androgen deprivation or systemic adjuvants for each man is unclear based on current evidence and prognostic and predictive parameters. Patient preferences play an important role in chosen therapy. It is hoped that future studies better capture all prostate cancer- and treatment- related morbidity to clarify the optimal therapy choices for each man with prostate cancer.

Keywords: Dose escalation; Hypofractionation; Prostate cancer; Radiation therapy.